IL-17A/IL-17F Double KO Mice Are Resistant to Lipopolysaccharide Induced Endotoxic Shock

Abstract

Aim: IL-17 family members, IL-17A and -17F are pro-inflammatory cytokines important for host immune modulation in infection and inflammatory diseases conditions. IL-17A has been shown playing a critical role in defense against bacterial infections and IL-17AF deficient mice (DKO) reported less protective. However, the role of IL-17 in endotoxic shock is largely undefined. Materials and Methods: Wild and DKO mice were intraperitoneally lipopolysaccharide (LPS) administered and their survival status was recorded. Neutrophil, -T cells in peritoneal fluids and pro- and anti-inflammatory cytokines, chemokines in serum in endotoxic wild and DKO mice were evaluated. Results: In this study, we observed a higher mortality rate in wild than DKO, in intraperitoneal LPS induced shock. Mortality was observed in correlation with increased pro-inflammatory cytokines and chemokines. We also observed a significant rise of -T cells in peritoneal cavity by LPS in wild, which is known to be a most potent source for IL-17 release and neutrophil recruitment at the site of infection. Neutrophil recruitment was shown as a protective phenomenon in murine in bacterial infection, but the same phenomenon was not observed in LPS induced sepsis. Conclusions: These findings suggest that neutrophil recruitment at infection site may be beneficial in case of direct bacterial exposure, but not in endotoxin exposure to host tissue. This study shades a comprehensive understanding of IL-17A/F functions in acute peritonitis followed by endotoxic shock that could be beneficial for selection of infection for IL-17 directed therapy.